IFFGD Professional Meeting: Advancing the Treatment of Fecal and Urinary Incontinence Through Research: Trial Design, Outcome Measures, and Research Priorities

Conference Cosponsors:International Foundation for Functional Gastrointestinal Disorders (IFFGD); and Office of Continuing Medical Education, University of Wisconsin Medical School

Participation and Purpose:This was a National Institutes of Health (NIH) supported interdisciplinary conference with international participation from over 180 gastroenterologists, urologists, colon and rectal surgeons, gynecologists, neurologists, geriatricians, pediatricians, nurses, psychologists, patient advocates, and representatives of the NIH.

The conference was initiated and organized by IFFGD to address issues surrounding incontinence.

The Conference took Place:Milwaukee, Wisconsin November 3-5, 2002

Incontinence is a disorder that affects men and women of all ages, often with devastating personal and societal consequences. It can lead to social isolation, loss of employment, and institutionalization. The economic impact has been estimated at $16 to $26 billion annually in the U.S. Fecal incontinence is estimated to affect 2%-7% of adults while urinary incontinence occurs in a third of adults and is severe enough to interfere with the quality of life and work in 6%. In the IFFGD survey, IBS in the Real World, 25% of respondents with IBS reported loss of bowel control.

To address issues surrounding incontinence IFFGD initiated and, with the Office of Continuing Medical Education of the University of Wisconsin Medical School, sponsored a meeting, Advancing the Treatment of Fecal & Urinary Incontinence Through Research: Trial Design, Outcome Measures, and Research Priorities, held November 3–5, 2002, at the Pfister Hotel, Milwaukee, Wisconsin.

This was a National Institutes of Health (NIH) supported interdisciplinary conference with international participation from over 180 gastroenterologists, urologists, colon and rectal surgeons, gynecologists, neurologists, geriatricians, pediatricians, nurses, psychologists, patient advocates, and representatives of the NIH. The purpose of the conference was to:

Summarize the state-of-the-science regarding epidemiology, pathophysiology, and available treatments for fecal and urinary incontinence;

Summarize available literature on outcome measures, predictors of successful treatment, and research design;

Identify the priorities for research from the perspective of each professional subspecialty concerned with the management of incontinence.

Over 40 faculty members presented on program topics that included:

Dimensions of the Problem: Prevalence and Impact

State-of-the-Art: Pathophysiology

Treatment Options for Fecal Incontinence

Treatment Options for Urinary Incontinence

Outcome Assessment

Predictors of Outcome in Treatment Trials

Priorities for Treatment Research from Different Professional Perspectives

Priorities for Treatment Research from Different Perspectives

Trial Design

General Discussion and Summation

Opening remarks at the meeting were presented by Nancy Norton, President of IFFGD and the driving force behind this symposium, and by William Whitehead, PhD, Chairman of the planning committee, which brought together a distinguished and diverse group of thought leaders and investigators for the conference.

This conference is an outgrowth of the first IFFGD sponsored meeting held in Milwaukee in 1999, the Consensus Conference on Treatment Options for Fecal Incontinence. The aim of the first meeting was to draft a statement to summarize available treatment options that could be used by primary care physicians in the treatment of patients. The Consensus Report was published in the Diseases of the Colon & Rectum (Volume 44, Number 1, January, 2001). While the report has had an impact on clinical practice, issues raised in the first conference led to the current meeting.

The research base of current health care delivery for incontinence is relatively limited. While there are many treatments available – medical, behavioral, and surgical – few randomized trials in support of these treatments have been published. The reasons for this include the wide range of causes and contributing factors to incontinence, multiplicity and differences in patient populations by age and by gender, and technical issues in validating as well as measuring outcomes, all of which have complicated consistent study designs. However, recent advances in methodology make new research opportunities possible. Additionally, the implementation by the U.S. National Institutes of Health (NIH) of two research networks focusing on urinary incontinence and on pelvic floor disorders has contributed to expanding the knowledge of how to conduct valid studies.

The ultimate goal of this meeting is to develop requests for research applications (RFAs) on the part of the NIH to fund research on the treatment of incontinence. The high quality of presentations and the interest demonstrated by the presenters and participants will surely play a positive role in making that happen-to the benefit of patients and everyone affected by this disorder.

Information about publications from the meeting will be posted on this site. We wish to thank the following participants and supporters of this important meeting:

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

The Office of Research on Women's Health, Office of the Director, National Institutes of Health (NIH)

Solvay Pharmaceuticals, Inc.

Abstracts

Nelson RL. Department of Surgery, University of Illinois College of Medicine at Chicago, USA.

Nursing home residence is by far the most prominent association with fecal incontinence, with a prevalence approaching 50%. In one major survey, urinary incontinence was the greatest risk factor for developing fecal incontinence, and fecal incontinence was the greatest risk factor for developing urinary incontinence. Immobility, dementia, and the use of physical restraints were also important risk factors. Specific diseases associated with fecal incontinence include diabetes, multiple sclerosis, Parkinson's disease, stroke, and spinal cord injury. The surgical procedures lateral internal sphincterotomy for anal fissure, fistulotomy, and ileal pouch reconstruction can result in fecal incontinence. Children who are born with congenital abnormalities, such as imperforate anus, often experience soiling for many years. Future studies to determine the prevalence and etiology of fecal and urinary incontinence will need to first define these conditions and eliminate referral bias. Epidemiologic investigations of both disorders should be performed jointly because the conditions are so often comorbid.

Failure to control the elimination of urine or stool causes psychological stress, complicates medical illnesses and management, and has major economic consequences. Patients often describe the impact of both fecal and urinary incontinence in terms of shame and embarrassment and report that it causes them to isolate themselves from friends and family. Incontinence frequently results in an early decision to institutionalize elderly relatives because families have difficulty coping with incontinence at home. Not surprisingly, there is an increase in symptoms of depression and anxiety in patients with incontinence as well as degradation in quality of life that has been documented by standardized assessment instruments. The direct health care costs for urinary incontinence are estimated to be 16.3 billion dollars per year (1995 costs). Separate cost estimates for fecal incontinence are not available. There is an acute need for methodologically sound studies to document the economic and personal impact of incontinence to develop guidelines for the allocation of health care resources and research funding to this major public health problem. This need is especially great for fecal incontinence, for which there is much less health care economic data than for urinary incontinence.

Fecal incontinence occurs when the normal anatomy or physiology that maintains the structure and function of the anorectal unit is disrupted. Incontinence usually results from the interplay of multiple pathogenic mechanisms and is rarely attributable to a single factor. The internal anal sphincter (IAS) provides most of the resting anal pressure and is reinforced during voluntary squeeze by the external anal sphincter (EAS), the anal mucosal folds, and the anal endovascular cushions. Disruption or weakness of the EAS can cause urge-related or diarrhea-associated fecal incontinence. Damage to the endovascular cushions may produce a poor anal "seal" and an impaired anorectal sampling reflex. The ability of the rectum to perceive the presence of stool leads to the rectoanal contractile reflex response, an essential mechanism for maintaining continence. Pudendal neuropathy can diminish rectal sensation and lead to excessive accumulation of stool, causing fecal impaction, mega-rectum, and fecal overflow. The puborectalis muscle plays an integral role in maintaining the anorectal angle. Its nerve supply is independent of the sphincter, and its precise role in maintaining continence needs to be defined. Obstetric trauma, the most common cause of anal sphincter disruption, may involve the EAS, the IAS, and the pudendal nerves, singly or in combination. It remains unclear why most women who sustain obstetric injury in their 20s or 30s typically do not present with fecal incontinence until their 50s. There is a strong need for prospective, long-term studies of sphincter function in nulliparous and multiparous women.

Delancey JO, Ashton-Miller JA. Department of Obstetrics and Gynecology, Institute of Gerontology, University of Michigan at Ann Arbor, 48109-0276, USA.

The anatomic structures that prevent stress incontinence, urinary incontinence during elevations in abdominal pressure, can be divided into 2 systems: a sphincteric system and a supportive system. The action of the vesical neck and urethral sphincteric mechanisms at rest constrict the urethral lumen and keep urethral closure pressure higher than bladder pressure. The striated urogenital sphincter, the smooth muscle sphincter in the vesical neck, and the circular and longitudinal smooth muscle of the urethra all contribute to closure pressure. The mucosal and vascular tissues that surround the lumen provide a hermetic seal, and the connective tissues in the urethral wall also aid coaptation. Decreases in striated muscle sphincter fibers occur with age and parity, but the other tissues are not well understood. The supportive hammock under the urethra and vesical neck provides a firm backstop against which the urethra is compressed during increases in abdominal pressure to maintain urethral closure pressures above rapidly increasing bladder pressure. The stiffness of this supportive layer is presumed to be important to the degree to which compression occurs. This supporting layer consists of the anterior vaginal wall and the connective tissue that attaches it to the pelvic bones through the pubovaginal portion of the levator ani muscle and also the tendinous arch of the pelvic fascia. Activation of the levator muscle during abdominal pressurization is important to this stabilization process. The integrity of the connection between the vaginal wall and tendinous arch also plays an important role.

This article addresses the diagnosis and treatment of pediatric fecal incontinence in 4 main categories: (1) Functional fecal retention, the withholding of feces because of fear of painful defecation, results in constipation and overflow soiling. Treatment includes dietary changes, use of laxatives, and cognitive and behavioral interventions such as toilet training, which diminishes phobia and provides positive reinforcement through a rewards system. (2) For functional nonretentive fecal soiling (encopresis), antidiarrheal agents can increase the consistency of stools and facilitate continence. Anorectal biofeedback for children has been proposed, but its efficacy remains unproven. Parents should be educated to conduct nonaccusatory toilet training and help children alleviate guilt and enhance self-esteem. Appropriately constructed trials are necessary to gauge the effect of adding prolonged use of enemas to an intensive toilet training program. (3) Surgery can correct minor congenital anorectal anomalies by identifying the external sphincter, separating the rectum from the genitourinary tract, and reconstructing the anus. However, there is great variation in postsurgical functional outcomes for anorectal malformations. Double-blinded, randomized controlled trials could help define the role of appendicostomy, cecostomy, sphincter reconstruction, colostomy, and artificial sphincters. (4) Children with spina bifida and fecal incontinence may benefit from techniques that teach them how to defecate. A continent appendicostomy (Malone procedure) is a promising treatment that completely cleanses the colon, increases the child's autonomy, and decreases the chance of soiling. A cecostomy can be performed surgically, endoscopically, or radiologically to provide some of the same benefits.

Urinary and fecal incontinence affect 50% or more of nursing home residents and frequently occur together because immobility and dementia are primary risk factors for both conditions. Many residents (40%-60%) show immediate improvement when provided with consistent toileting assistance, which compensates for the immobility and dementia risk factors that prevent them from toileting independently. Residents who are responsive to assistance can be identified with a 2-day run-in trial during which prompts are provided every 2 hours to encourage toileting. This run-in trial also provides an opportunity to use protocols to identify and treat other reversible causes of incontinence (e.g., urinary tract infection, fecal impaction) and to diagnose problems with bladder or anorectal functioning. The effects of toileting assistance on the frequency of fecal incontinence, while significant, are less dramatic than those reported for urinary incontinence, primarily because of constipation. Fortunately, noninvasive interventions have been identified that address most of the risk factors common to both constipation and fecal incontinence. Trials are needed to evaluate treatments that integrate noninvasive interventions directed toward the use of laxatives or constipating agents, low toileting frequency, low food and fluid intake, and physical activity to improve constipation and fecal incontinence in nursing home residents. The scientific documentation of the efficacy of such a noninvasive intervention and the labor costs of implementing these measures can lead to major changes in how nursing home care is funded and provided.

Although surgical therapy has been shown to be an effective treatment of anal incontinence, few properly controlled randomized studies have confirmed its efficacy or compared it with biofeedback or other less invasive forms of treatment. Overlapping sphincteroplasty, the most common procedure, seems to confer substantial benefits on patients with sphincter disruptions. However, recent data suggest that results following sphincteroplasty deteriorate with time. There is also disagreement about whether pudendal nerve conduction studies can be used to predict outcome after surgical repair. Salvage options for patients with refractory fecal incontinence include passive or electrically stimulated muscle transfer procedures, implantation of an inflatable artificial anal sphincter, and sacral nerve stimulation. Stimulated graciloplasty is the most commonly used muscle transfer procedure; good to excellent results are reported from a small number of high-volume centers, but multicenter trials with less experienced surgeons have shown a high morbidity rate associated with the procedure. The artificial anal sphincter provides good restoration of continence for most patients who retain the device, but a significant explantation rate due to infection or local complications remains problematic. Sacral nerve stimulation has shown promising early results with minimal associated morbidity. There is a critical need for controlled long-term studies that use objective data collection methods, standardized outcome measures, and validated quality-of-life assessment instruments.

Scarlett Y. Division of Gastroenterology and Heptaology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill 27599, USA.

Diarrhea and constipation are known risk factors for fecal incontinence. This report reviews how to diagnose and medically treat patients with chronic diarrhea, chronic constipation with overflow incontinence, and incontinence resulting from rectal mucosal prolapse secondary to hemorrhoids. Antidiarrheal agents (including loperamide, diphenoxylate, and difenoxin) and the tricyclic antidepressant amitriptyline improve continence in patients with diarrhea-associated incontinence. Other antidiarrheal agents are under investigation. The mechanism is believed to be decreased intestinal motility and stool frequency resulting in more formed stools. Increases in anal canal resting pressure may also contribute to improvement in continence. Adverse effects are constipation from excessive use. In addition to antidiarrheal drugs, fiber supplements may improve incontinence associated with diarrhea. Transient, benign cases of constipation usually respond to increasing fluid intake and dietary fiber, improving mobility, or eliminating the concurrent use of constipating drugs. For mild to moderate constipation, bulking agents, laxatives, and stool softeners are used cautiously so as not to excessively loosen stools and exacerbate anal incontinence. Laxatives have been shown to improve continence, possibly through the mechanism of eliminating fecal impaction. Prolapsing hemorrhoids may partially obstruct defecation and cause soilage from the passage of fecal material, mucus, or blood. With endoscopic banding, a ligator is attached to an endoscope and a tight band is placed around the enlarged vein, causing the hemorrhoid to thrombose.

Biofeedback has been advocated as first-line therapy for patients whose symptoms of mild to moderate fecal incontinence have not responded to simple dietary advice or medication. Three main modalities have been described: (1) use of an intra-anal electromyographic sensor, a probe to measure intra-anal pressure, or perianal surface electromyographic electrodes to teach the patient how to exercise the anal sphincter; (2) use of a 3-balloon system to train the patient to correctly identify the stimulus of rectal distention and to respond without delay; and (3) use of a rectal balloon to retrain the rectal sensory threshold, usually with the aim of enabling the patient to discriminate and respond to smaller rectal volumes. Although a systematic review found that biofeedback eliminated symptoms in up to one half of patients and decreased symptoms in up to two thirds, these studies suffered from methodological problems, a lack of controls, and a lack of validated outcome measures. No studies have compared different exercise instructions, measured patient compliance with those instructions, or determined any trends in symptom response to the exercises prescribed. A recent study by the author suggests that patient-therapist interaction and patient coping strategies may be more important in improving continence than performing exercises or receiving physiological feedback on sphincter function. Better-designed randomized, controlled trials are needed to evaluate different exercise programs and different elements of biofeedback. Development and validation of outcome measures are important, and predictors of outcome and effects in patient subgroups, especially elderly and neurologically impaired patients, should also be investigated.

Urinary incontinence affects many Americans, predominantly women. The majority of health care costs are spent on absorbent products, and diagnosis and treatment consume significant additional resources. Many factors interact with urinary incontinence-including medications, health conditions, and other pelvic floor disorders. There has been no meaningful research on prevention of urinary incontinence. The majority of research has focused on treatment, often with medical approaches or surgery. Surgery for urinary incontinence is largely limited to treatment of stress urinary incontinence. Nearly 300 procedures have been proposed, but very few have been the subject of significant, high-quality research. Three groups of surgical procedures (and their variants) have been utilized over the past decades: urethropexy, colposuspension, and the sling. Effective surgery appears to result from enhancing sphincteric closure during increases in intra-abdominal pressure. There are only a few studies that compare these procedures to one another. Many surgical procedures are adopted based on expert opinion and novel, untested concepts. A significant number of postoperative patients experience continued incontinence despite "cure" of stress incontinence. Research in the field of surgery for urinary incontinence can be facilitated by development of better diagnostic aids, better outcome measures, and techniques that allow standardization of interventions and testing procedures (including urodynamics). The role of industry needs close scrutiny-because novel, untested techniques and materials are frequently introduced without careful human subjects testing. Although surgery will continue to play an important role in the treatment of urinary incontinence for Americans, high-quality studies are urgently needed in this field.

Treatment options for urinary incontinence include behavioral techniques, pharmacologic agents, and surgical procedures. Caregivers use pharmacotherapy heavily because of its availability, immediacy of results, and convenience. However, only pharmacotherapy for urge incontinence has advanced to the level at which several drugs that have undergone rigorous scientific testing using randomized controlled trials have received FDA approval; these are the antimuscarinic and anticholinergic/direct smooth muscle relaxant drugs. However, promising new drugs targeting other receptors are under investigation. There is no FDA-approved drug for stress incontinence or overflow incontinence. Pharmacologic clinical trials for urinary incontinence are no different than pharmacologic trials in other areas. A randomized controlled trial is the best approach for documenting effectiveness and safety. A rigorous trial should include identification of primary and secondary outcomes. The measurement tools of outcomes must be reliable and validated. Preferably, the severity level of urinary incontinence should be established, and measurement of effectiveness must include durability. Not only must side effects be identified, but their impact on the quality of life must be quantified. An exciting area in pharmacologic treatment of urinary incontinence is the method of drug delivery. In addition to sustained release oral medication, the transdermal patch and the intravaginal route are starting to be used in clinical practice. The intravesical route is still in the investigational phase. Pharmacologic research for urinary incontinence is now entering an exciting time because technologic advances are creating new agents with more precise targeting and more sophisticated methods of delivery are being developed and tested.

Behavioral treatments improve bladder control by changing the incontinent patient's behavior, especially his or her voiding habits, and by teaching skills for preventing urine loss. These treatments are effective for most outpatient men and women with stress, urge, or mixed incontinence. The average reduction in the frequency of incontinence ranges from 57% to 86%. In long-term care settings, treatment is generally more challenging and yields more modest results. The advantages of behavioral interventions include the absence of side-effects, patient comfort, and high levels of patient satisfaction. Although most patients who receive behavioral treatment achieve significant improvement, most are not completely dry. Thus, there is a need for research to explore ways to enhance the effectiveness of these conservative therapies. Combining behavioral treatment with other treatments may have additive effects. Research is also needed to understand better the mechanisms of therapeutic change, the best methods for teaching pelvic floor muscle control, the optimal exercise regimens, the predictors of outcome, and the efficacy of behavioral treatments in men. Although behavioral interventions are more accepted today than 20 years ago, they are still not widely available or integrated into most clinical practices, and we know little of how effective they will be in these settings. Thus, it will be important to develop and evaluate creative modes of delivery, such as group intervention (especially by nonphysician providers), in a variety of clinical settings.

Fecal incontinence is a symptom attributable to a variety of disorders affecting one or more factors that maintain continence. Objective assessments should complement symptom assessments as outcome measures in therapeutic trials; conceivably, these assessments may also predict the response to therapy. Consistent with existing trends, most therapeutic trials should incorporate anal sphincter pressures and rectal sensation as outcome variables, paying meticulous attention to techniques. Rectal sensation is increased after pelvic floor retraining by biofeedback therapy in fecal incontinence; however, the predictive value of improved anal pressures after biofeedback has not been clearly established. Other factors maintaining continence can be assessed by newer approaches. In addition to assessing rectal sensation, a barostat also measures rectal compliance; alterations in rectal compliance modulate rectal perception. Particularly appropriate end points for trials involving surgical repair are sphincter integrity, assessed by endoanal ultrasound or magnetic resonance imaging (MRI), and puborectalis and pelvic floor motion, assessed by dynamic MRI. Despite disagreement about which technique is superior for evaluating the internal sphincter, MRI performs the same or better than ultrasound for assessing the external sphincter. The utility of measuring pudendal nerve latencies as a marker of pudendal nerve injury is limited; needle electromyography provides a sensitive measure of denervation and can usually identify myopathic damage, neurogenic damage, or mixed injury. These standardized, reproducible assessments of the multifaceted mechanisms maintaining fecal incontinence should be incorporated as outcome variables in therapeutic trials of fecal incontinence.

Nygaard I. Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City 52242, USA.

Physiologic outcome measures are divided into 2 groups: (1) measures that visualize, quantify, and analyze the reasons for urine loss and (2) measures that assess the anatomy and neuromuscular function of continence-related structures. Few of the frequently used physiologic outcome measures have been rigorously tested. The evidence in support of their use derives mainly from case series information and expert opinion. Perineal pad testing is used to quantify urine leakage associated with stress incontinence. One-hour pad tests are commonly used for clinical trials and office visits; 24- and 48-hour tests are more reliable and reproducible. Urodynamic testing simultaneously assesses bladder and urethral function during bladder filling and emptying to help guide therapy and identify patients who are at risk for surgical failure. Testing usually includes (1) uroflowmetry, an assessment of voiding without catheters in place; (2) cystometry, which assesses bladder sensation, capacity, compliance, and inappropriate detrusor activity during filling; (3) urethral pressure profilometry, to gauge urethral closing pressures and pressure transmission ratios; (4) leak-point pressure, the minimum intra-abdominal pressure required to cause incontinence, which serves as a measure of urethral function; and (5) pressure flow studies, which diagnose obstruction by evaluating detrusor pressure and flow rate during voiding. The cotton swab test is used to assess bladder neck mobility after surgical interventions. Using the Pelvic Organ Prolapse Quantification system, researchers can describe pelvic support in a standardized, reproducible fashion. Applications of ultrasonography and magnetic resonance imaging in urogynecology are promising but remain in the investigational stages.

Rockwood TH. Division of Health Services Research and Policy, School of Public Health, University of Minnesota, Minneapolis 55455-0392, USA.

This article reviews self-reporting instruments to measure severity and quality of life in fecal incontinence. Severity instruments assess the frequency, type, and amount of stool loss and the impact of fecal incontinence on coping mechanisms and lifestyle/behavioral change. Non-weighted instruments use simple numerical totals to gauge severity; however, the use of vague quantifiers to describe severity can make the results highly subjective. In weighted surveys, every possible response (indicating the frequency of each type of incontinence) is multiplied by a weight that reflects the average severity assigned by a representative group of patients (or physicians), and the weighted responses are added to compile a total score. When variables such as coping mechanisms and lifestyle changes are included in severity questionnaires, the results tend to reflect patient functioning more than severity and should be interpreted cautiously. Quality-of-life scales assess variables that are not directly observable and are highly subjective. Quality-of-life scales are divided into 3 categories: (1) generic scales permit the measurement of gross change and compare the experience of the target population to other populations; (2) specialized scales are most useful in trying to isolate effects of specific variables, such as depression; and (3) condition-specific quality-of-life scales measure the relationship between specific medical conditions or treatments, and quality of life outcomes. Future research should focus on the need for weighting, further evaluation of the use of coping mechanisms as an indicator of severity, and how to integrate measures of urgency. In the area of quality of life, "modules" are needed that can be appended to established instruments to help assess and compare the experience of specific populations.

Symptoms of incontinence are common, particularly among older people, and incontinence can have a severe effect on the quality of life of some individuals at any age. A number of treatments are available, most of which aim to reduce the occurrence of incontinent episodes or to limit the effects of the disorder on everyday life. In research and clinical practice, it is essential that the symptoms and effects of incontinence be properly assessed and recorded. The only valid means of measuring patients' perspectives is through the use of psychometrically robust self-report questionnaires. Incontinence may be experienced as part of the symptom complex of a range of conditions (e.g., benign prostatic diseases or fistulas), and the effect of incontinence on quality of life varies depending on the severity of the condition and other psychosocial and medical factors. Questionnaires with acceptable levels of psychometric testing are identified and recommended for use in clinical practice and research investigations according to the following categories: (1) questionnaires to assess symptoms of incontinence, (2) generic health-related quality-of-life questionnaires to assess the effect of incontinence on quality of life, and (3) incontinence-specific measures to assess the effect and bothersomeness of incontinence on quality of life.

Cross-cultural research often involves physicians, nurses, and other health care providers. In studies of fecal and urinary incontinence, cross-cultural research has been applied to quality-of-life comparisons, and instruments have been translated to foreign languages for use in other countries. This report presents some of the principal methodological issues and problems associated with translating questionnaires for use in cross-cultural research in a manner relevant to clinicians and health care practitioners who are aware that, unless these potential problems are addressed, the results of their research may be suspect. Translation is the most common method of preparing instruments for cross-cultural research and has pitfalls that threaten validity. Some of these problems are difficult to detect and may have a detrimental effect on the study results. Identification and correction of problems can enhance research quality and validity. A method for translation and validation is presented in detail. However, the specific validation method adopted is less important than the recognition that the translation process must be appropriate and the validation process rigorous.

This report reviews the advantages and disadvantages of 2 types of outcome assessment regularly used in the literature on incontinence: (1) global assessments of symptoms or relief and (2) ratings of specific symptoms of incontinence. Global assessments are usually used when the target condition involves multiple and variable symptoms. They are easy for patients to understand and yield data that seem to correspond closely to the target of the treatment (e.g., symptom severity). The 2 major scaling approaches used in clinical symptom assessment, categorical scaling and cross-modality matching of symptom intensity to line length (visual analogue scales), are reviewed for their reliability and validity. Numerical scales provide the advantage of a large number of possible ratings (usually 9-100) and are intuitively easy to use. All methods of symptom assessment using patient recall are subject to potential reporting bias. Measures of current symptoms, although less biased, may not reflect ongoing symptom levels, and current symptom levels tend to influence patients' recall of both symptom severity and medication counts. However, patient-initiated ratings are relevant to assessing "real-time" symptoms in incontinence trials, and even single retrospective ratings of "usual" symptom intensity may actually be an adequate reflection of the average symptom severity (at least for chronic pain). Applying subjective, predetermined criteria for success, such as the provision of "adequate relief," allows researchers to closely mimic clinical situations and use a cutoff point ("threshold") specifically associated with the condition and treatment being investigated. Devices such as personal digital assistants that can cue subjects for information at set or random intervals, record multiple types of responses, and accurately assess compliance with data recording should help facilitate future research.

Prather CM. Department of Gastroenterology and Hepatology, St. Louis University School of Medicine, Missouri 63110, USA.

Identification of physiologic factors that predict response to fecal incontinence therapy would be helpful in choosing the optimal treatment and advising patients on the likelihood of a successful outcome. However, few physiologic parameters have been consistently identified as important in predicting response to either biofeedback or surgery. The process of isolating these factors has been hampered by heterogeneity in the definition of fecal incontinence, lack of consensus on what constitutes a successful outcome, lack of follow-up data, variations in the way "standard" treatments are implemented, and lack of properly powered randomized controlled trials. Among the physiologic variables that studies have generally found to be predictive of successful outcomes in biofeedback treatment are the threshold for external anal sphincter contraction after treatment, the inclusion of sensory training in treatment, and a reduction in volume for the first sensation after treatment. Factors that have not been found to be important in predicting outcome following biofeedback retraining include the duration of fecal incontinence, pudendal nerve damage, patient age, symptom severity, pretreatment anal canal pressures, and results of anal ultrasonography. The presence of some degree of anorectal sensation is the only preoperative assessment that has been found to be predictive of response to surgical therapy. It is recommended that outcome measures for fecal incontinence be more clearly defined, that future biofeedback studies elaborate the predictive value of pretreatment anorectal sensation and the response to sensory retraining, and that postsurgical measurements such as anal squeeze pressure and sphincter length be taken into account.

Goode PS. Division of Geriatric Medicine and Gerontology, Department of Medicine, University of Alabama at Birmingham, 35233, USA.

Demographic, medical, and physiologic predictors of behavioral treatment and pharmacotherapy success would be useful in selecting treatments for specific patients with urinary incontinence based on their histories, physical examinations, and urodynamic profiles. The author performed a systematic review of clinical trials of behavioral treatment or pharmacotherapy for urinary incontinence. Most postulated predictors (age, type and duration of incontinence, medications including diuretics and estrogen, obstetric history, physical examination, and urodynamic findings) were not predictive of treatment outcomes. For behavioral therapy, male gender predicted worse outcomes in 1 study, but it was not a predictor in 2 other studies. Greater severity of incontinence predicted positive outcomes in 2 studies, negative outcomes in 3 studies, and had no predictive value in 5 studies. Prior treatment for incontinence predicted poorer outcomes in 2 studies of urge incontinence but was not predictive in a study of stress incontinence. Prior surgical treatment predicted better outcomes in 1 study of urge incontinence in women but was unrelated in 4 studies. Male gender, depression, or the use of assistive devices for ambulation predicted poorer outcomes in homebound older persons. For pharmacotherapy of urge incontinence, older age, female gender, and greater incontinence severity were associated with poorer outcomes in 1 study. Age was unassociated with outcomes in another study. Thus, the literature on predictors of outcomes of behavioral and drug treatment for urinary incontinence is inconsistent and does not provide guidelines for treatment selection. More studies, with large samples, that use multivariate regression analysis to examine predictors of outcomes are needed.

Heymen S. Department of Medicine, Division of Digestive Diseases, University of North Caroline at Chapel Hill, 27599-7080, USA.

An estimated 15% to 30% of adults over the age of 60 years have urinary incontinence, which is often reported as severe. Although psychological symptoms, especially anxiety and depression, are often associated with urinary incontinence, it seems likely that psychological distress is not a cause but a consequence of suffering from the condition. Cognitive deficits that directly interfere with the neurologic function of the bladder and/or diminish the ability to communicate appear to be important contributors to urinary incontinence. The incidence of fecal incontinence is high in children up to the age of 9 years and ranges from 7% to nearly 10% in adults over the age of 65 years. Although it has been suggested that psychological symptoms can cause fecal incontinence, data are lacking to support a causative association. Psychological disorders and incontinence of urine and feces appear to be common comorbidities. Studies are needed to determine whether the incidence of psychological symptoms in persons with incontinence is comparable for those who seek treatment and those who do not and to compare psychometric and quality-of-life measures before and after treatment to help determine the role of psychological symptoms in persons with fecal and urinary incontinence.

Biofeedback techniques used to treat urinary and fecal incontinence lack standardization. Most early protocols used a pressure device placed within the vagina or anal canal, or electromyographic (EMG) sensors in the same locations, to measure the external anal sphincter (EAS) or pelvic floor muscle (PFM) contractile function, and most early studies provided feedback from a single physiological transducer. The goal was to improve bowel and bladder control by improving EAS or PFM contractile function. Protocols that have resulted in the most consistent reductions in urinary incontinent episodes used 2 or more channels of physiological information to reinforce stable abdominal and bladder pressures concurrently with PFM contraction. For fecal incontinence, more significant treatment results were derived when protocols measured (1) patient perception of sensory cues associated with rectal distention and potential loss of stool, (2) short-latency EAS contraction when perceiving rectal distention, (3) inhibition of (extraneous muscle) activity that would increase intra-abdominal pressure during EAS contraction, and (4) reinforcement of sustained (up to 30 seconds) contractions rather than only brief 1- to 2-second contractions. Limited data support the use of surface abdominal EMG measures as indices of extraneous muscle activity associated with increased intra-abdominal pressure and anal or vaginal EMG probes to obtain measures of PFM function. Better results may also be obtained when there are at least 4 training sessions, when daily home exercises are prescribed, and when the therapist is well trained and experienced. These inferences are based for the most part on indirect evidence, and more studies are needed that compare different treatment protocols.

Whitehead WE. Center for Functional GI and Motility Disorders, University of North Carolina at Chapel Hill, 27599-7080, USA.

There are 4 sources of bias in clinical trials: investigator bias, patient expectation (placebo response), ascertainment bias (inadvertent selection of an unrepresentative sample), and nonspecific effects such as the normal waxing and waning of symptoms over time and the quality of the doctor-patient relationship. In drug trials, these biases are adequately controlled by comparing active to inert pills, randomly assigning subjects to treatments, blinding both the investigator and subject to group assignment, and testing subjects at multiple sites. However, there are special problems with conducting clinical trials of behavioral or psychological interventions that render these controls inadequate. It is impossible to blind the experimenter to which treatment is active, it is difficult to identify a control treatment that is inactive but just as credible to the subject, and doctor-patient relationship variables are more important than in drug trials. The inability to blind the experimenter can be circumvented by having an independent, blinded investigator assess the outcome, and doctor-patient effects can be controlled by using multiple, experienced therapists. The most difficult problem, identifying an appropriate control treatment, can be solved by adhering to 2 principles: the control treatment should be plausible, and it should not have a significant impact on the mechanism that is thought to explain the effectiveness of the investigational treatment. Investigators should confirm that these 2 goals have been achieved by monitoring expectation of benefit with a treatment credibility questionnaire, measuring changes in process variables (variables that reflect the presumed mechanism of treatment), and monitoring differential dropout rates.

Surgical trials differ in several critical aspects from pharmaceutic trials because they are invasive and the procedure itself may carry a significant risk. The surgical procedure cannot be fully specified in advance; although the general approach may be the same, the exact methods used during surgery may differ. Surgeons may have different levels of skill and experience with the techniques; experience is known to affect success rates. Sham surgeries are difficult to justify ethically, yet they have been successful in showing that accepted surgical procedures were not efficacious. Double masking participants in a surgical trial may be difficult; for example, we cannot mask the surgeon. There is also a need to minimize or avoid bias. Therefore, greater flexibility is needed in the design of surgical trials than in the design of pharmaceutic trials. Some of this flexibility is possible through the use of more sophisticated statistical designs. At times, it is necessary to separate the provider of the treatment (the surgeon) from the evaluator of the success of the treatment (a different physician, research nurse, or study coordinator).

PMID: 14978655 [PubMed - indexed for MEDLINE]

Gastroenterology.2004 Jan;126(1 Suppl 1):S169-71The perspective of a gynecologist on treatment-related research for fecal incontinence in women.

Fecal incontinence affects between 1% and 16% of women, with prevalence increasing with age. The most common cause of fecal incontinence in otherwise healthy women is damage to the anal sphincter(s) during childbirth. As such, the most important tool in the "treatment" of fecal incontinence is its prevention, which should be the first research priority for gynecologists. Routine midline (median) episiotomy has no place in modern obstetrics; when episiotomy must be performed for obstetric indications, use of mediolateral episiotomy should result in fewer anal sphincter injuries than use of midline episiotomy. Additional research questions that gynecologists hope to address are as follows. (1) When anal sphincter injury occurs at delivery, what is the most effective method of repair? Even when repair is performed, women frequently have symptoms of altered bowel function ranging from fecal urgency to frank fecal incontinence. (2) Is it possible to improve the relatively poor results of a strictly surgical repair? Does pelvic muscle rehabilitation (performed either after vaginal delivery or after secondary repair remote from delivery) add significantly to the outcome of women after anal sphincteroplasty? (3) Another more general research priority is to understand the shared and independent factors in the pathophysiology of fecal and urinary incontinence so as to identify modifiable risk factors in women.

PMID: 14978656 [PubMed - indexed for MEDLINE]

Gastroenterology.2004 Jan;126(1 Suppl 1):S172-4.The perspective of a neurologist on treatment-related research in fecal and urinary incontinence.

Fowler CJ. Institute of Neurology and Institute of Urology, UCL, National Hospital for Neurology and Neurosurgery, London, England.

Afferent innervation is important in sensing the degree of bladder fullness and in forming the input limb to involuntary detrusor contractions in neurogenic and probably also non-neurogenic detrusor overactivity. It is likely that homologous mechanisms are involved in control of the bowel. Accumulating evidence now suggests that in conditions of bladder hypersensitivity as well as non-neurogenic detrusor overactivity, there is up-regulation of unmyelinated nerve fibers expressing both the vanilloid receptor and purinergic receptors. The development of a selective neurotoxin that could successfully "deafferent" the bladder would have major therapeutic consequences. Women who respond best to neuromodulation through sacral nerve stimulation are those with a primary disorder of sphincter relaxation and a very large capacity without sensations of urgency or a hyperactive sphincter. For these women, neuromodulation may counteract the inhibitory effects of overactive sphincter afferents on the detrusor, and determination of the central nervous system level at which this response occurs may provide an explanation for the paradoxical finding that both urge incontinence and urinary retention are responsive to this intervention. Experimental evidence suggests that the "procontinence" reaction consists of an inhibitory effect on the detrusor and presumably the lower rectum resulting from contraction of the pelvic floor and the anal or urethral sphincter. Development of methods of enhancing the inhibitory reflex effect could lead to improved voluntary control of micturition and defecation for patients with neurogenic bladder overactivity or spinal cord lesions.

The International Foundation for Functional Gastrointestinal Disorders (IFFGD) is a nonprofit education and research group. Founded in 1991, the IFFGD provides information and advice to patients around the world with fecal incontinence and other gastrointestinal disorders, educates physicians through medical symposia and other activities, funds and undertakes research, and provides testimony to Congress about the necessity of furthering research activities related to fecal incontinence through the National Institutes of Health. The IFFGD advocates research directed toward more comprehensive identification of quality-of-life issues associated with fecal incontinence and improved assessment and communication of treatment outcomes related to quality of life, standardization of scales to measure incontinence severity and quality of life, assessment of the utility of diagnostic tests for affecting management strategies and treatment outcomes, development of new drug compounds offering new treatment approaches to fecal incontinence, development and testing of strategies for primary prevention of fecal incontinence associated with childbirth, and further understanding of the process of stigmatization as it applies to the experience of individuals with fecal incontinence.

PMID: 14978658 [PubMed - indexed for MEDLINE]

Gastroenterology. 2004 Jan;126(1 Suppl 1):S180-5.Priorities for treatment research from different professional perspectives.

Whitehead WE, Wald A, Norton NJ. Division of Gastroenterology and Hepatology, Center for Gastrointestinal and Motility Disorders, University of North Carolina at Chapel Hill 27599-7080, USA.

The consensus conference "Advancing the Treatment of Fecal and Urinary Incontinence Through Research" had as one of its goals the development of a comprehensive list of research priorities. Experts from all disciplines that treat incontinence-gastroenterology, pediatric gastroenterology, urology, urogynecology, colorectal surgery, geriatrics, neurology, nursing, and psychology-and patient advocates were asked to identify their highest priorities for treatment-related research. Meeting participants were shown the aggregated list and invited to propose additional priorities. Treatments for fecal incontinence (biofeedback, sphincteroplasty, antidiarrheal and laxative medications, and sacral nerve stimulation) require validation by randomized, controlled trials. For urinary incontinence, the greatest need is to compare pharmacological, behavioral, and surgical treatments. Trials assessing combined treatments (e.g., biofeedback plus surgery vs. surgery alone or biofeedback alone) are also needed. New drugs are needed that target anal canal resting pressure in fecal incontinence and hypersensitivity to distention in urge urinary incontinence. It may be possible to substantially reduce the incidence of incontinence through modification of obstetric practices (e.g., avoiding episiotomies or offering elective cesarean delivery to high-risk patients), providing pelvic floor exercises before childbirth, and educating patients to avoid straining during defecation. For the elderly, practical behavioral and pharmacological treatments are needed that can postpone or avoid institutionalization. Social science research may identify ways to counteract the social stigma of fecal incontinence and assist physicians in providing patients with more comprehensive and understandable information on the risks associated with different treatment options.